Various types of optical sensors utilizing SPR measurement have been reported since the first gas detection and biosensing sensor based on SPR was developed by Nylander et al., “Surface plasmon Resonance for gas detection and biosensing” by Lieberg, Nylander and Lundstrom in Sensors and Actuators, Vol. 4, page 299. Traditional sensing technique for extracting information from SPR is primarily concerned with analyzing angular and wavelength properties of a reflected light beam within the resonant reflectance dip.
Nelson et al. presented the first SPR sensing based on optical phase detection (Sensors and Actuators B, 35-36, 187-191, 1996). The phase quantity has a steep slope response and therefore offers the potential for at least 3 times greater resolution than sensors based on conventional angle and wavelength modulation.
However, Nelson's phase detection system is very sensitive to mechanical vibrations and phase errors incurred in the system may become problematic. System stability issues of Nelson's system limit its applications. Phase detection improvements under “noisy” environment have been widely studied.
Recent research's attention to the SPR sensing has shifted to measuring the SPR phase shift, because the resonant phase behavior exhibits a steep jump, which leads to the potential in achieving extremely high sensitivity.
The most recent work was presented by Chien-Ming Wu et al., who reported a heterodyne interferometric system for the investigation of phase variation during surface plasmon resonance (Sensors and Actuators B 92, 133-136, 2003). The system used a combined SPR with total internal reflection (TIR) so that an extra phase shift caused by TIR may be added to a detected signal. In addition, a reference optical path is employed in the system to suppress unwanted noise. But the drawback is that the sensor response is measured by monitoring the phase shift versus incident angle, which requires highly stable mechanical parts. Also, the reference optical path is not totally identical to the signal path. Therefore, common-mode noise may still exist in the differential measurement.
Sheridan analyzed the phase behavior of an SPR waveguide sensor (Sensors and Actuators B 97, 114-121, 2004). The system employed a Mach-Zehnder interferometer (MZI) configuration with two sensing branches. Since only one branch was exposed to index variation, unwanted refractive index changes common to two branches such as temperature variation are said to be suppressed. This device was found to provide a higher sensitivity than the conventional single-waveguide configuration.
FIG. 6 shows a conventional sensing device with an SPR sensor of the Kretschmann configuration, of which the detailed description and discussion can be found in the articles by H. P. Ho, et al., “Real-time optical biosensor based on differential phase measurement of surface plasmon resonance” (BIOSENSORS & BIOELECTRONICS, 20 2177-2180, 2005), and by S. Y. Wu, et al., “Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach-Zehnder configuration” (OPTICS LETTERS 29, 2378-2380, 2004). Their entire disclosure is incorporated herein by reference.
As shown in FIG. 6, a light beam from an He-Ne laser source 1′ is divided into two beams Is and Ir by a 50:50 beam splitter 2′. In a signal path, the beam Is enters a silver sensing surface 41′ of a sensing head 4′, while the beam Ir is reflected by a mirror surface 3′ in a reference path. The two beams are recombined at a beam splitter 5′ and form interference pattern. After passing through a Wollaston prism 6′, SPR images are captured by a detection device 7′, and then are input to a data processor 8′ for analysis.
Although the differential SPR phase approach as shown in FIG. 6 has improved measurement accuracy significantly, similar to other SPR phase techniques, the problem existing in the SPR phase approach is that the distribution of SPR phases over the sensing surface is not recorded. The information obtained from the mapping of surface reactions which can be directly inferred from the SPR phase distribution is necessary and important for many bio-reaction monitoring applications. For example, users may want to perform biosensing of a range of analytes from a single sample simultaneously. The capability of the SPR phase imaging is particularly important. In addition, given that the phase imaging imposes more stringent requirements on an optical instrument due to a relatively low signal to noise ratio and a low frame rate (i.e. low data collection speed) achievable by a common imaging device such as CCDs, it is necessary to further develop the current differential SPR phase technique, in order to provide a better signal to noise ratio for the imaging measurement, while enabling the phase to be stepped as required at a speed appropriate to the imaging device.